Tryptophan is an amino acid which is essential for cell proliferation and survival. It is required for the biosynthesis of the neurotransmitter serotonin, the synthesis of the cofactor nicotinamide adenine dinucleotide (NAD), and is an important component in the immune system response (“immune escape”) to tumors. Depletion of levels of tryptophan is associated with adverse effects on the proliferation and function of lymphocytes and diminished immune system response.
The enzyme indoleamine-2,3-deoxygenase (IDO) is overexpressed in many human tumors. IDO catalyzes the initial, rate-limiting step in the conversion of tryptophan to N-formylkynurenime. Moreover, IDO has been implicated in neurologic and psychiatric disorders including mood disorders as well as other chronic diseases characterized by IDO activation and tryptophan degradation such as viral infections, for example, AIDS, Alzheimer's disease, cancers including T-cell leukemia and colon cancer, autoimmune diseases, diseases of the eye such as cataracts, bacterial infections such as Lyme disease, and streptococcal infections.
Accordingly, an agent which is safe and effective in inhibiting the function of IDO would be an important addition for the treatment of patients with diseases or conditions affected by the activity of the enzyme.